This is an application for a K23 Mentored Patient-Oriented Career Development Award entitled "Time Course of Subthalamic Deep Brain Stimulation." The primary goal of the proposed research is to delineate new therapeutic mechanisms of action of Subthalamic nucleus deep brain stimulation (STN DBS). STN DBS is a highly effective, widely used treatment for Parkinson's disease (PD). Therapeutic effects of STN DBS persist for some time after stimulation ceases. Mechanisms of action of STN DBS, particularly of such "persistent" effects, are not well understood. Experiments are proposed in which STN DBS effects on PD symptoms are measured over time when STN DBS is turned on and off in patients with STN stimulators implanted for treatment of PD, to test the hypothesis that the mechanism of lingering effects differs from that of "immediate" effects seen during stimulation. Experiments are integrated with a computer simulation of neuronal biophysics to test the hypothesis that DBS-induced synaptic plasticity accounts for lingering effects. The candidate has clinical training in neurology/movement disorders, including PD and in DBS, including STN DBS for PD. He has research training in motor neurophysiology, in animal models. The goal of the proposed Career Development Award is to enable him to merge his clinical and research training in a program of patient-oriented research focusing on the use of brain stimulation to study movement disorders and improve their treatment, using computer modeling techniques to relate cellular processes to clinical observable therapeutic effects. To this end, the candidate seeks training in 1) basal ganglia physiology and biophysics of DBS, 2) computer modeling techniques 3) patient-oriented research. [unreadable]